Dr. Ally
Clinical question: Is cefepime-taniborbactam effective in treating complicated urinary tract infections (UTIs)?
Background: Complicated UTIs, such as acute pyelonephritis, have a significant health impact, with 600,000 hospitalizations in the U.S. each year. Given the routine use of antibiotics to treat UTIs, antibiotic resistance has become common. Adding taniborbactam to cefepime inhibits beta-lactamase activity, allowing cefepime-taniborbactam to be effective to treat Enterobacterales species (such as Escherichia coli, Proteus spp, Klebsiella spp, and Enterobacter cloacae) and Pseudomonas aeruginosa bacteria. This study compared cefepime-taniborbactam with another commonly used antibiotic, meropenem, to assess the former’s safety and efficacy when treating complicated UTIs.
Study design: Phase 3, double-blinded, randomized trial
Setting: 68 sites in 15 countries
Synopsis: 661 adult patients with complicated UTIs were randomized and 436 were in the microbiologic intention-to-treat (microITT) group. Over a third of the patients were 65 years and older. Patients were included in this study if their urine culture grew only one gram-negative bacterial species (at least 105 colony-forming units/mL), not resistant to meropenem. Patients were excluded if they had received anti-microbial therapy prior to the trial, had a glomerular filtration rate less than 30 mL/min/1.73m2, had an allergy to a beta-lactam antibiotic, were a renal transplant recipient, or had a diagnosis of prostatitis, renal or perinephric abscess, or severe hepatic impairment. Patients received cefepime-taniborbactam 2.5 g or meropenem 1 g every eight hours for seven days, with possible extension of treatment up to 14 days for patients with bacteremia (13.1% of microITT group). Oral step-down therapy was not permitted. Primary efficacy was a microbiologic and clinical success when testing for cure on trial days 19 to 23. For this study, microbiologic success was defined as urine culture results of pathogen growth of ≤103 colony-forming units/mL. Clinical success was defined as the resolution of symptoms. Cefepime-taniborbactam was deemed to be superior to meropenem in microbiologic and clinical success (95% confidence interval, 3.1 to 22.2, P=0.009), with a composite success rate of 70.6% for patients who had received cefepime-taniborbactam compared to 58% in those who received meropenem. Cefepime-taniborbactam has the same safety profile as meropenem, with similar adverse effects, namely headache, hypertension, diarrhea, nausea, and constipation.
Bottom line: Cefepime-taniborbactam was superior to meropenem in treating complicated UTIs growing Enterobacterales species or Pseudomonas aeruginosa.
Citation: Wagenlehner FM, Gasink LB, et al. Cefepime-taniborbactam in complicated urinary tract infection. N Engl J Med. 2024;390(7):611-22.
Dr. Ally is a clinical professor of medicine in the division of hospital medicine and a physician advisor at the University of California in San Diego.